This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Populations consuming high levels of soy, as in many Asian countries, have lower levels of ovarian hormones, lower rates of breast cancer, and reduced mammographic density than populations consuming typical Western diets. These observations may in part be explained by our clinical studies that found ovarian hormone levels of premenopausal women to be lowest while they were consuming a diet that provided 15% energy from soymilk containing weakly estrogenic isoflavones. No adverse effects were observed. Further questions are whether isoflavones are the critical components influencing breast cancer risk and whether they do so by affecting other reversible risk markers for breast cancer, such as breast density. We propose to conduct a randomized, double-blind placebo controlled 2-arm study, with 200 premenopausal women (N=100/arm) to: (1) determine the effects of continuing exposure to isoflavones on serum levels of ovarian hormones and breast density and bone density and (2) assess potential adverse effects of chronic soy isoflavone exposure (hyperplastic epithelial cells in nipple aspirates, amenorrhea and low bone density). 200 women (30 to 42 years old, not on contraceptive, with normal mammograms) will be randomly allocated to take soy isoflavones in pills (120 mg of total aglycones/day) (treatment) or placebo (maltodextrin 120 mg/day) (placebo) 5 days per week for 2 years. We predict that the soy diet will reduce breast density and possibly bone density, and that these reductions in breast density will correlate with isoflavone intakes.